The primary aim of this proposal is to further our efforts to improve the treatment and care of adult patients with malignant brain tumors through continued participation as a fully funded member in the Phase I and II clinical investigations of the New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium. This consortium utilizes the resources, expertise and patient populations of 10 outstanding medical institutions with experienced, multidisciplinary brain tumor programs and demonstrated ability to evaluate novel therapeutic agents and modalities in this challenging patient population. During our past 6 years of partially funded provisional membership in NABTT, Wake Forest University has demonstrated: (1) an outstanding ability to accrue adult patients with newly diagnosed or recurrent high grade astrocytomas to Phase I and II clinical trials of novel therapeutic agents; (2) an outstanding ability to collect, collate, monitor and transmit all manners of clinical data, including tissue samples, and to do so in an exemplary and timely fashion; and (3) scientific leadership in the conception, development and implementation of new treatment paradigms for patients with malignant brain tumors. This effort is an extension of the sustained tradition of excellence in clinical research and trial design on the part of the NCI-designated Comprehensive Cancer Center of Wake Forest University which has demonstrated expertise in concept development, biostatistics, pharmacology, data management and patient accrual over the past 25 years. A second aim of this proposal is to share our institutional interest in and ability to collect, utilize and distribute brain tumor specimens and other clinical material with institutions interested in the molecular events responsible for glioma development and progression, and the immunohistochemical and molecular prognostic markers of tumor behavior and response to therapy. We continue to expect that the novel observations which arise from these efforts will lead to improvements in both the overall survival and quality of life of our patients afflicted with these tumors.